Mammary carcinoma metastasis is the leading cause of cancer deaths in adult women. We will develop an animal model for mammary carcinoma metastasis that closely mimics human breast carcinoma utilizing the chemically-transformed rat 13762 adenocarcinoma. By selecting variant tumor cell populations capable of enhanced spontaneous metastasis from mammary fat pads to regional lymph nodes as well as regional lymph nodes plus major organs, and cloning these cell lines, we will be able to compare 13762 cell lines and clones of varying malignancies and metastatic properties for alterations in cell surface morphologies, antigens, glycoproteins, glycosaminoglycans, glycolipids and degradative enzymes. We will examine the role of surface fibronectin in blood-borne tumor cell attachment to endothelial cells and endothelial extracellular matrix. Host hormonal and immune status and their role in metastatic spread will also be investigated, and we will determine the sensitivities of various metastatic lines and clones of 13762 to some chemotherapeutic drugs in vitro in order to develop more effective approaches for secondary tumor therapy.